The objective of the project is to identify and characterize molecules that regulate cell proliferation in normal and neoplastic cells and to understand the mechanism of action of these molecules. We also intend to develop tissue-specific reagents by isolating monoclonal antibodies to intermediate filament proteins. We have found that many malignant cells in culture do not require platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) for growth. The neoplastic cells do not possess cell surface PDGF receptors, but do have EGF-specific receptors. Conditioned medium from the tumor cells contains an activity that competes with 125I-labeled PDGF for binding to the PDGF receptor. Growth-stimulating activity is also present in conditioned medium. An anti-PDGF antibody removes PDGF-competing activity and growth-stimulating activity from the conditioned medium. Five different anti-intermediate filament protein antibodies have been isolated. An antivimentin antibody only stains mesenchymal tissue. Three different anticytokeratin antibodies recognize different classes of epithelial cells. One stains only the suprabasal portion of squamous epithelium, another stains the full thickness of squamous epithelium and ductular epithelium, and a third stains all nonsquamous epithelium but fails to stain squamous epithelium. An antineurofilament protein antibody stains only neurons of the central and peripheral nervous systems. These antibodies are useful in distinguishing lymphomas from carcinomas, melanomas from carcinomas, melanomas from lymphomas, and neuroblastomas from lymphomas. We have also isolated a monoclonal antibody to smooth muscle actin that recognizes smooth muscle cells and smooth muscle tumors. (N)